Prodigiosin induces apoptosis and inhibits autophagy via the extracellular signal-regulated kinase pathway in K562 cells
Prodigiosin induces apoptosis and inhibits autophagy via the extracellular signal-regulated kinase pathway in K562 cells
复制标题
灵菌红通过细胞外信号调节激酶途径诱导 K562 细胞凋亡并抑制自噬
DOI：
10.1016/j.tiv.2019.05.003
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发表时间：
2019-10-01
影响因子：
3.2
通讯作者：
Pu, Yuepu
中科院分区：
文献类型：
--
作者：
Ji, Shuangbin;Sun, Rongli;Pu, Yuepu
芥子皂苷含有三吡咯骨架，在多种细胞系中显示出令人印象深刻的抗癌潜力。大量的研究表明，芥子红素诱导细胞凋亡及其机制。然而，很少有报道考虑芥红素对细胞自噬的影响以及细胞凋亡与自噬的关系。在这里，我们通过细胞增殖、流式细胞术、caspase活性和western blot分析，研究了prodigiosin是否通过细胞外信号调节（ERK）信号通路影响K562细胞的凋亡和自噬。我们用PD184352抑制ERK信号通路来验证该通路在prodigiosin介导的过程中的作用。结果表明，prodigiosin抑制K562细胞增殖，增加活性氧（reactive oxygen species， ROS），诱导凋亡，抑制K562细胞自噬。此外，活性氧清除剂n-乙酰- l-半胱氨酸（NAC）部分阻止了prodigiosin诱导的K562细胞凋亡，但没有减少prodigiosin抑制的自噬。此外，在K562细胞中，prodigiosin处理降低了c-Jun n -末端激酶（JNKs）和P38的磷酸化，激活了ERK信号通路。当PD184352阻断ERK1/2磷酸化后，prodigiosin诱导的细胞凋亡和自噬抑制显著降低。综上所述，这些结果表明ERK信号通路参与了prodigiosin诱导的细胞凋亡和prodigiosin抑制的自噬。
Prodigiosin contains a tripyrrole skeleton and shows impressive anticancer potential in multiple cell lines. Numerous studies have been conducted on prodigiosin-induced apoptosis and the related mechanisms. However, few reports have considered the effects of prodigiosin on autophagy and the relationship between apoptosis and autophagy. Here, we examined whether prodigiosin affected apoptosis and autophagy through the extracellular signal-regulated (ERK) signaling pathway in K562 cells, employing cell proliferation, flow cytometry, caspase activity, and western blot analyses. Inhibition of the ERK signaling pathway with PD184352 was conducted to verify the role of this pathway on prodigiosin-mediated processes. Our findings revealed that prodigiosin inhibited the proliferation of K562 cells, increased reactive oxygen species (ROS), induced apoptosis and inhibited autophagy in K562 cells. Additionally, the ROS scavenger, N-Acetyl-L-cysteine (NAC), partially prevented prodigiosin-induced apoptosis but did not reduce prodigiosin-inhibited autophagy in K562 cells. Furthermore, prodigiosin treatment in K562 cells reduced the phosphorylation of c-Jun N-terminal kinases (JNKs) and P38, and activated ERK signaling pathway. When ERK1/2 phosphorylation was blocked by PD184352, prodigiosin-induced apoptosis and the inhibition of autophagy decreased significantly. Taken together, these results demonstrated that the ERK signaling pathway was involved in prodigiosin-induced apoptosis and prodigiosin-inhibited autophagy.